HLA LOH Detection via Liquid Biopsy: A Blood-Based Predictive Biomarker Assay for Precision Immuno-Oncology

/ABSTRACT T-cell-receptor (TCR)-mediated immunotherapy, including immune checkpoint inhibitor (ICI) therapy, is becoming a mainstream cancer treatment modality, but the majority of patients still do not respond to these therapies. Human leukocyte antigen class I loss of heterozygosity (HLA LOH) is a mechanism of resistance to TCR- mediated immunotherapies and is found in the tumors of 1/6 of all cancer patients. In some cancer types the prevalence of HLA LOH is higher, and in non-small-cell lung cancer (NSCLC), approximately 40% of patients have tumors that harbor HLA LOH. To improve immunotherapy treatment outcomes for NSCLC patients, it is crucial to utilize a diagnostic assay to detect whether a patient’s cancer has HLA LOH. Tempus offers an assay that detects HLA LOH in cancer patients using a tumor-based approach which received FDA Breakthrough Device Designation and is now utilized for patient enrollment screening in two clinical trials. However, a tumor- based assay requires surgical biopsy, which is not always feasible. A blood-based liquid biopsy for detecting HLA LOH in patients with solid malignancies would allow for detecting the biomarker without the need for collecting a tumor biopsy sample, but there is no commercial HLA LOH liquid biopsy assay for solid malignancies on the market. Our startup, Sesh, is commercializing the first liquid biopsy assay for detecting HLA LOH in cancer patients with solid tumors. Sesh’s liquid biopsy assay, RELOAD (Restriction Element Loss Of Allele Detection), is a cell-free DNA (cfDNA) next-generation sequencing (NGS) assay co-invented by our CEO Dr. Andrew Sinkoe while he was a postdoctoral fellow at the National Cancer Institute (NCI) Center for Immuno-Oncology. Sesh has licensed the liquid biopsy technology underlying RELOAD from the NCI Technology Transfer Center (TTC) via a Commercial Evaluation License (CEL) and is applying for a Phase I SBIR-TT to continue the commercialization process for the technology. Sesh plans to conduct concordance studies and analytical validation studies that will lead to the assay’s usage in the clinic, and our goal is to eventually obtain FDA approval for the assay via a PMA to bring RELOAD to market. This SBIR-TT Phase I focuses on implementing RELOAD in NSCLC as this cancer type has a high prevalence of HLA LOH and patients with this type of cancer have been shown to have significantly worse responses to ICI therapy when harboring HLA LOH compared to patients with HLA intact. Project Number: 1U43CA302144-01A1 | Fiscal Year: 2025 | NIH Institute/Center: National Cancer Institute (NCI) | Principal Investigator: Andrew Sinkoe | Institution: SESH INCORPORATED, San Diego, CA | Award Amount: $406,500 | Activity Code: U43 | Study Section: Special Emphasis Panel[ZCA1 RPRB-L (M3)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11254232